Irradiation chamber for photoactivation patient treatment system

ABSTRACT

A removable U.V. light array assembly for use in a photoactivatable agent, patient treatment system wherein photoactivatable agents, in contact with patient blood cells, are irradiated extracorporeally and then returned to the patient.

This is a continuation, of application Ser. No. 834,258, filed Feb. 27,1986 now abandoned, which is a continuation-in-part application of U.S.Ser. No. 665,834, filed Oct. 29, 1984, now U.S. Pat. No. 4,573,960.

FIELD OF THE INVENTION

This invention relates to the field of treating cells withphotoactivatable compounds and radiation which activates the compoundthereby affecting the cells and specifically, relates to clinicallyuseful systems for the extracorporeal treatment of blood cells,especially leukocytes, including a disposable source of U.V. radiationin a removable light array assembly.

BACKGROUND OF THE INVENTION

It is well-known that a number of human disease states may becharacterized by the overproduction of certain types of leukocytes,including lymphocytes, in comparison to other populations of cells whichnormally comprise whole blood. Excessive or abnormal lymphocytepopulations result in numerous adverse effects to patients including thefunctional impairment of bodily organs, leukocyte mediated autoimmunediseases and leukemia related disorders many of which often ultimatelyresult in fatality.

U.S. Pat. Nos. 4,321,919; 4,398,906; 4,428,744; and 4,464,166 to Edelsondescribe methods for treating blood whereby the operation or viabilityof certain cellular populations may be moderated thereby providingrelief for these patients. In general, the methods comprise treating theblood with a dissolved photoactivatable drug, such as psoralen, which iscapable of forming photoadducts with DNA in the presence of U.V.radiation. It is believed that covalent bonding results between thepsoralen and the lymphocyte nucleic acid thereby effecting metabolicinhibition of the thusly treated cells. Following extracorporealradiation, the cells are returned to the patient where they are thoughto be cleared by natural processes but at an accelerated pace believedattributable to disruption of membrane integrity, alteration of DNAwithin the cell, or the like conditions often associated withsubstantial loss of cellular effectiveness or viability.

Although a number of photoactivatable compounds in the psoralen classare known, 8-methoxy psoralen is presently the compound of choice. Aneffective radiation for this compound, and many psoralens in general, isthe ultraviolet spectrum in the range of approximately 320 to 400nanometers, alternatively referred to as the U.V.A. spectrum. As thedevelopment of photoactivatable compounds proceeds, it may be expectedthat changes in the preferred activation radiation spectrum will benecessary. Suitable selection of radiation sources will, of course,increase treatment efficiency and is contemplated as an obviousoptimization procedure for use with the inventions disclosed herein.

Although Edelson's methods have been experimentally shown to providegreat relief to patients suffering from leukocyte mediated diseases,numerous practical problems require solutions. In particular, Edelsonfails to provide a suitable apparatus for applying radiation to thecells, e.g. via a treatment station, in an economical and efficaciousmanner, or a system for incorporating a treatment station providing forthe treatment of a patient in a clinically acceptable format.

Conventional techniques for photoactivating compounds associated withcells have relied on a plurality of devices including flasks, filtrationcolumns, spectrophotometer cuvettes, and petri dishes. The sample to beirradiated is added to the containers and the container placed adjacentto the radiation source. Such systems tend to be laboratory curiositiesas they fail to provide the necessary safeguards intrinsically necessarywhere patient bodily fluids are concerned, particularly since thesefluids must be returned to the patient thereby necessitating strictavoidance of contamination. Further, such methods tend to be volumelimited, are characterized by many mechanical manipulations and aregenerally unacceptable from a clinical and regulatory viewpoint. It isan object of the present invention to provide methods and apparatussuitable for use with the Edelson methods to overcome the limitationsassociated with the conventional expedients.

Copending applications U.S. Ser. No. 650,602, now abandoned describes apractical device for coupling the radiation provided by commerciallyavailable light sources, such as the so-called "black-light" fluorescenttubes, to cells for treatment by Edelson's photoactivated drug methods.In summary, the disposable cassette described therein comprises aplurality of fluorescent tube-like light sources such as the U.V.A.emitting Sylvania F8TS/BLB bulb, which are individually, coaxiallymounted in tubes of larger diameter which are, in turn, coaxiallymounted in sealing arrangement within second outer tubes of even largerdiameter thereby forming a structure having two generally elongated,cylindrical cavities about each radiation source. The inner cavitypreferably communicates with the atmosphere thereby facilitating coolingof the radiation source. The second tube forming the outer cavityfurther comprises inlet and outlet means for receiving and discharging,respectively, the cells to be irradiated. A plurality of thesestructures are "ganged" and suitable connections made between inlets andoutlets of adjacent members to provide for serpentine flow of cellsthrough each outer cavity. Thus, continuous flow of the cells throughthe plurality of cavities surrounding the centrally disposed radiationsources facilitates thorough treatment of the cells. Additional,detailed description of the Taylor device may be obtained by directreference to U.S. Ser. No. 650,602 now abandoned.

To be fully practical, the Taylor device requires a clinicallyacceptable instrument to house the device and to provide the cells to betreated in an appropriate form. Such an instrument is the object of theinventions described in U.S. Pat. Nos. 4,573,960, 4,568,328, 4,578,056,4,573,961, 4,596,547, 4,623,328 and 4,573,962, fully incorporated hereinby reference. While the instruments described therein work well, it isan object of the instant application to describe improved systemscapable of implementations, in advanced fashions, the medical treatmentprinciples first taught by Edelson.

It is another object of the present invention to provide still furtherimprovements in greater patient safety and comfort while reducingtreatment time and coast, by utilizing a newly designed disposableirradiation chamber in an appropriate instrument which incorporates anew, advanced photoactivating light array assembly.

It is yet another object to provide an improved instrument which meetsthe above criteria while maintaining the positive attributes of theprior system; compactness, mobility, completeness, fully automated andmonitored, coupled with ease of operation.

It is a further related object of this invention to provide, in contrastto the time consuming batch like processing of the prior system,disposable light array assembly for use with a continuous on-linepatient treatment system wherein collection, separation, and celltreatment occur simultaneously, thereby reducing treatment time andincreasing patient safety and comfort.

BRIEF DESCRIPTION OF THE DRAWINGS

These and still other objects of the invention will become apparent uponstudy of the accompanying drawings wherein:

FIG. 1 illustrates a preferred configuration of the system duringcollection, separation, and treatment;

FIG. 2 shows a front elevational view of the flat plate irradiationchamber mating with a recirculation pump; and photoactivating lightsource array;

FIG. 3 shows a bottom view of the preferred embodiment of the lightarray assembly with the irradiation chamber mounted therein;

FIG. 4 shows a perspective view of the most preferred embodiment of theirradiation chamber; and

FIG. 5 shows a side view of the FIG. 4 embodiment.

SUMMARY OF THE INVENTION

In accordance with the principles and objects of the present inventionthere is provided a disposable irradiation chamber for use with apatient treatment apparatus. The patient treatment system provides for"on-line" extracorporeal photoactivation of a photoactivatable agent incontact with patient cells, particularly blood, by collecting andseparating blood on a continuous basis, returning to the patientundesired blood portions obtained during separation while the desiredportion is photoactivatably treated and thereafter returning the thuslytreated cells to the patient. As a result of this novel approach, thetreatment system of the instant inventions optimizes and minimizestreatment time by concurrently conducting various aspects of aphotoactivation treatment process which were previously performedsequentially.

More specifically, the apparatus collects and separates blood on acontinuous basis as it is withdrawn from the patient and returnsunwanted portions to the patient while concurrently energizing thephotoactivating irradiation sources in a disposable light arrayassembly. The energized light assay photoactivates the photoactivatableagent in contact with the desired blood portion while the agent and thecells (or other patient fluid) is contained within the flat plateirradiation chamber of the chamber-pump block of the instant invention.Following photoactivation, the treated cells may then be facilelyreturned to the patient utilizing a drip chamber gravity feed infusionline incorporated in a dedicated tubing set.

The irradiation chamber of the instant invention provides for efficientactivation of photoactivatable agents by irradiation from light arrayassembly described U.S. Ser. No. 834,256. In the most preferredembodiment, irradiation of both sides of the irradiation chamber takesplace concurrently while still permitting facile removal of the chamber.A most preferred embodiment of the chamber further comprises a solidstate device for controlling the use of the irradiation chamber therebyensuring patient safety and device efficacy.

DETAILED DESCRIPTION

FIG. 1 shows various aspects of the system developed forextracorporeally treating a patient based in part upon the scientificdiscoveries of Edelson. While the specific design, construction andoperation of the apparatus 10 is the result of a number of separateinventions some of which form the subject matter of previously describedissued patents and copending commonly assigned applications includingU.S. Ser. No. 834,292 entitled "Concurrent On-Line Irradiation TreatmentProcess"; U.S. Ser. No. 834,293 entitled "Electronic Device ForAuthenticating and Verifying Disposable Elements"; U.S. Ser. No. 834,294entitled "Disposable Temperature Probe For Photoactivation PatientTreatment System"; U.S. Ser. No. 834,303 entitled "Improved ValveApparatus For Photoactivation Patient Treatment System"; U.S. Ser. No.834,256 entitled "Light Array Assembly For Photoactivation PatientTreatment System"; U.S. Ser. No. 834,257 entitled "Pump Block ForInterfacing Irradiation Chamber To Photoactivation Patient TreatmentSystem"; U.S. Ser. No. 834,260 entitled "Demountable Peristaltic PumpFor Photoactivation Patient Treatment System"; and U.S. Ser. No. 834,259entitled "Zero Insertion Force Socket For Photoactivation PatientTreatment System"; the relevant parts of which are fully incorporatedherein by reference, it is believed a brief description may be helpful.

The operation of the device and performance of the methods can bedivided into two basic phases or modes, depicted in part by FIG. 1. Thefirst phase is shown substantially in FIG. 1 wherein the patient isconnected at the point shown, preferably by venipuncture or the likemethods well-known and developed to a high degree in the dialysis arts.Patient blood, as it flows to the apparatus 10 (alternately referred toherein as the puvapheresis apparatus or system) is preferably infused,under control of pump 11, with an anticoagulant agent contained incontainer 20 hung from stand 15. Control of the flow of patient blood tothe remainder of apparatus 10 is controlled largely by clamping means16a which has the dual function of also controlling flow in the reversedirection as well as flow to return container 21. Clamp 16a acts as an"or" valve.

Normally the blood flows through tubing 24 through blood pump 12(preferably a roller pump such as that described in U.S. Pat. No.4,487,558 to Troutner entitled "Improved Peristaltic Pump" andincorporated herein by reference) into continuous centrifuge 13. Thiscontinuous centrifuge, available commercially from suppliers such asDideco, Haemonetics and others, is preferably capable of continuouslyseparating blood based on the differing densities of the individualblood components. "Continuously", as used herein means that, as bloodflows into the centrifuge through line 24, it accumulates within therotating centrifuge bowl and is separated so that low density componentsare emitted after a certain minimum volume has been reached within thecentrifuge bowl and as additional blood is added. Thus, the continuouscentrifuge in effect acts as a hybrid between a pure on line system anda pure batch system. This occurs because the centrifuge bowl has acapacity to hold most, if not all, of the most dense portion, typicallyerythrocytes or red blood cells while emitting lower density portionssuch as plasma and leukocytes (white blood cells) as whole blood iscontinuously added. At some point, however, the reservoir volume of thecentrifuge is filled with the higher density components and furtherseparation cannot be effectively obtained. Prior to that point, theoperator, by viewing the uppermost portion of the centrifuge bowlthrough the centrifuge cover, can detect qualitatively when thecentrifuge emits plasma (as opposed to priming solution), leukocyteenriched portions and the remainder, i.e., nonleukocyte enrichedportions, including erythrocyte enriched portions. Based on theoperator's observations, he or she enters through control panel 19(specifically via panel portion 42) the identification of the individualblood portions as they are emitted from the centrifuge. This informationis entered by keys 44 (e.g., PLASMA, BUFFY COAT or leukocyte enrichedportion) on control panel 19, and in response thereto, the apparatus 10controls valve mechanism 16c to direct the leukocyte enriched portionand a predetermined volume of plasma into plasma-leukocyte enrichedcontainer 22 while excess plasma, air, priming fluids, erythrocytes etc.are directed to container 21.

Once the centrifuge is no longer capable of further separation due tothe attainment of its capacity, the operator directs that the bowl beemptied by suitable data key entry on panel 19 and the fluid contents ofcentrifuge 13 are advantageously pumped into return container 21 bymeans of pump 12 under the control of valves 16a and c. The foregoingsteps may be repeated a number of times or cycles before the desiredvolume of leukocyte enriched blood and plasma is obtained for furthertreatment, in each instance the undesired portions being collected inreturn container 21.

Between cycles, the fluids, including erythrocytes which have beenpumped into return bag 21 are gravity fed back to the patient through adrip infusion operation and controlled by valve 16b. It is preferredthat gravity feed be employed rather than pumping the blood back to thepatient via pump 12 in order to avoid potential pressurization problemsat the infusion insertion site at the patient, and also to avoid foamingor other air related dangers.

As may be already appreciated, when initially set up, the centrifugebowl and line 24 may be expected to contain sterilized air which ispreferably removed by suitable priming operations advantageouslyaccomplished by utilizing the anticoagulation agent in container 20;both the air and a portion of priming solution being collected incontainer 21.

Also to be noted is the predetermination of the desired leukocyteenriched volumes and plasma volume to be collected within container 22as well as the number of cycles to be employed to collect same. Thesevolumes are selected largely in accordance with the individual volumecapacities of the containers as well as the treatment chamber to bedescribed later. Accordingly, these volumes are set in order topreferably optimize handling efficiency and to ensure patient safety.For instance, one preferred selection would include the followingsettings: 250 ml total buffy coat or leukocyte enriched portion and 300ml of plasma to be collected within container 22. This might require anynumber of cycles, preferably on the order of three or four, bearing inmind that the more cycles that are selected, the lower the total volumeof blood withdrawn from the patient at any one time. If blood collectionmeets the minimum capacity limits of the centrifuge bowl, the patient'scapacity to withstand temporary blood volume depletions and thetreatment procedure in general is increased. Further, more cycles willpermit more discriminating selection of leukocyte enriched blood as itis emitted from the centrifuge. The buffy coat and plasma volumes aswell as the number of cycles are typically physician selected.Accordingly, the controls governing these selections are preferablyplaced within the apparatus 10, such as behind door 18a where theirinadvertent alteration may be advantageously avoided, especially sinceno operator interaction is normally required with respect to these datainputs.

The leukocyte enriched container 22 is connected via tubing line 34 tothe flat plate treatment irradiation chamber behind assembly door 17with a return line 35 to reservoir container 22.

Referring now to FIG. 2, the leukocyte enriched blood, plasma, andpriming solution contained in reservoir 22 (FIG. 1) is delivered throughline 501 to the inlet 209 of the flat plate irradiator 513. The cavityin the flat plate is relatively "thin" (e.g. on the order ofapproximately 0.04") in order to present large surface area of leukocyterich blood to irradiation and reduce the self-shielding effectsencountered with lower surface area/volume ratios. The fluid flowsupward through the serpentine pathway in cavity 503 in the irradiationchamber to the outlet 210. While a serpentine pathway is preferred inorder to avoid or minimize stagnant areas of flow, other arrangementsare contemplated. Outlet tubing 511 passes through the pump block 504[described in greater detail in U.S. Ser. No. 834,257], affixed to theend of the flat plate irradiator 513, and then connects to return line35 which returns fluids from the irradiation chamber to container 22.

Recirculation pump rotor 203, which is located internally in the machine(mounting not shown), engages the tubing in the pump block in thesemi-circular tract 508 and thereby provides and controls therecirculating flow of fluid, from container 22 up through irradiationchamber 513 and back to container 22. In a preferred embodiment, a metalsegment 220 in outlet tubing line 511 incorporates a thermocouple 213[described more fully in U.S. Ser. No. 834,294] which permits monitoringof the fluid temperature.

Sterile air initially contained in the irradiation chamber cavity 503 isdisplaced by entering fluid and stored in the top of container 22. Byreversing the rotation of recirculation pump rotor 203, the air storedin container 22 can be pumped back into the outlet 210 of the chamber513 thereby displacing all fluids back into container 22. Once fluid isinitially delivered to container 22, the recirculation pump rotor 203 isenergized filling the irradiation cavity 503 and displacing sterile airto container 22. When the irradiation chamber is filled and BUFFY COATbutton 44 on panel 19 is pressed, the light array assembly whichsurrounds the irradiation chamber is energized. Continued operation ofthe recirculation pump rotor 203 continuously recirculates the leukocyteenriched fluid from container 22 through the chamber for receivingphotoactivating radiation from the energized light array assembly 401(FIG. 3) and back to container 22.

FIG. 3, illustrating the light array assembly 401 from a bottom view,shows two rows, in the most preferred embodiment although one row can beused, of radiation sources 400 powered through contacts 216. Suchsources are conveniently chosen so that illumination is reasonablyconstant over the entire irradiation cavity 503 (FIG. 2). Suitablesources include the Sylvania FR15"T8/350BL/HO/180° with 2011 phosphorusbulb which is in the so-called fluorescent tube form. As is apparentfrom FIG. 3, the irradiation chamber 513 slides between the rows ofradiation source 400 so that pump block 504 engages pump rotor 203driven by motor 250. Other aspects of the light array assembly 400 arediscussed in U.S. Ser. No. 834,256.

Thus, photoactivation of the leukocyte enriched fluid by irradiation isinitiated at the outset of, and continues during and after thecollection and separation process. In the most preferred mode, the lightarray assembly will comprise sources of ultraviolet radiation, mostpreferably of the UVA type for activating the photoactivatable agentpresently of choice, 8-methoxy psoralen.

In operation, and with respect to FIG. 1, the exposure time on the righthand portion of the panel 19 is set in accordance with physiciandetermined criteria. The central control means of the apparatus 10,calculates and displays on one section of the panel 19, via centralprocessing unit and memory stored software, the exposure time remainingat the onset of irradiation treatment and as the treatment progresses.Another section of the control panel also includes three operatorcontrolled entry data keys whereby the operator can de-energize thelight assembly array and stop the recirculation process if desired.Actual photoirradiation treatment preferably commences automaticallyunder control of the central processing unit when fluid is firstdirected to container 22, continues while leukocyte enriched bloodportion from container 22 is pumped through the irradiation chamber backinto container 22, and terminates when the present exposure time hasexpired. At that time, the light array assembly is de-energized and therecirculation pump reverses emptying the contents of the irradiationchamber 513 into container 22.

Thereafter container 22 is ideally removed to stand 15 where it isconnected to tube 36, provided on the common drip chamber 21a alsoassociated with return container 21, for reinfustion of the treatedblood portion into the patient.

To enhance patient safety and decrease the risk of contamination to thepatient blood and blood portions, each time a connection is made orbroken, it is preferably only done once. Thus, container 22 wouldideally have four connection points or ports; one for the collection ofthe leukocyte enriched blood portion, two for connection to the flatplate irradiation chamber (feed and return), and the fourth forconnection to the drip chamber (21a) for reinfustion of treated blood tothe patient.

With further reference to FIG. 1, the control panel 19 of the apparatus10 is shown with the keyboard entry buttons 44, each ideally having alight which, when lit, preferably indicates the stage of the operation.Advantageously, the keyboard entry buttons 44 are preferably placed insequential order thereby assisting the operator in learning the systemand performing the steps in the correct order. Indeed, the centralcontrol means will preferably be programmed to prevent out of stepsequences from being implemented. A visual display indicates the volumeof leukocyte enriched blood collected in container 22.

Panel 19 will preferably also contain a power switch, as well as a bloodpump speed control whereby the operator may select the speed with whichthe blood is withdrawn from the patient and pumped through the systemduring collection. Also preferably included is an alpha-numeric displayfor indicating the machine's status and identifying alarm conditionsthroughout system operation. Optional accessory status lights,preferably provided in green, yellow, and red colors, provide at aglance the overall operating status of apparatus 10. Further included isa mute/reset button for quieting an audible alarm activated in the eventan alarm condition occurs and operator input is required.

Other features may be readily apparent from the drawings such as thepreferable inclusion of casters and caster brakes for enhancing themobility of the apparatus. Further, side panel 23 will preferablyinclude mechanical means (e.g. hanging pegs and the like) for assistingin the securement of container 22. It may also optionally be outfittedwith a transparent or translucent opening 18b in the area beneathcontainer 22 for providing at a glance information regarding theillumination status of the irradiation treatment chamber during thetreatment phase. For instance, if the window is of sufficient size, theoperator may readily determine that each irradiation source within thetreatment chamber is illuminated as desired. Naturally, the materialcomprising such window is preferably selected in order to containharmful radiation, if any, within apparatus 10.

The aforedescribed photopheresis blood treatment apparatus is madelargely possible by an automated control method for directing the bloodportions, derived from the continuous centrifuge, into particularcontainers. The automated method performs in accordance with presetvolume determinations which are manually entered behind panel 18apursuant to a physician's direction. These predetermined volumes specifythe volume to be contained within container 22 by setting forth thevolume of plasma and the volume of leukocyte enriched blood portion tobe directed thereto. Additionally included within these conditionsetting parameters is preferably the ability to set forth the number ofcycles of blood collection and separation required or desired in orderto obtain the desired blood volumes.

The volumes collected are determined in accordance with the blood volumepumped by the blood pump. This may be suitably monitored andcommunicated to the central control means by specifically monitoring thenumber of step pulses input to the pump to cause rotations of the bloodpump. Typically, 200 pulses results in one revolution. Rotation may alsobe conveniently monitored such as by attachment of a slotted disk to theshaft and the passage of slots determined by an optical sensor meanssuch as that described in U.S. Pat. No. 4,623,328 (fully incorporatedherein) and by monitoring shaft rotation. The resultant periodic signalmay be conveniently correlated with speed and number of rotations bycircuit designs well-known in the art. The number of rotations by any ofthe foregoing methods coupled "with the known volume pumpingcharacteristics of the pump", will provide the necessary informationregarding the volume of blood pumped. It will readily be appreciatedthat the sensors need not be optical but may be electronic or mechanicalinstead.

In actual operation, a most preferred procedure would be as follows. Theoperator presses teh PRIME CENT. key on control panel section 19 whichprimes the tubing set, the blood pump, and the centrifuge with theanticoagulation solution contained in container 20. Displaced sterileair is collected in container 21. When priming solution emerges from theexit of the centrifuge, the operator presses PRIME U.V. key on controlpanel section 42 which closes the tubing line to container 21 and opensthe tubing line to container 22 by means of valve 16c. Recirculationroller pump rotor 203 is energized to prime the flat plate irradiationchamber and displce sterile air to container 22. The priming processstops automatically after a preset volume of fluid is delivered tocontainer 22.

Blood collection is started by the operator pressing START key oncontrol panel 19. Thereafter, blood is withdrawn from the patient andpumped by the blood pump into the rotating centrifuge. As the bloodenters the centrifuge, it displaces the priming solution which emergesfirst in accordance with its preferably lighter density. This primingsolution is automatically directed into container 22 until a presetvolume is delivered, after which the emerging solution is redirected tocontainer 21 by means of valve 16c. At some point, the priming solutionwill be completely displaced from the rotating centrifuge and plasmawill begin to emerge. This emergence may be directly observed throughport 14 whereupon the operator presses the PLASMA key on control panel19. Thereafter, the central control means automatically directs theplasma into container 22 by altering valve 16c keeping track of thevolume as it does so since the volume entering the centrifuge equals thevolume emerging therefrom. This continues until the operator indicatesthe leukocyte enriched portion, i.e. buffy coat has begun by pressingthe respective data entry key in control panel section 42 whereupon, theleukocyte enriched portion continues to container 22, however, thevolume so directed is monitored as buffy coat volume. Alternately, ifall of the predetermined plasma volume is collected prior to theemergence of the buffy coat, then the central control meansautomatically diverts, by valve 16c, the emerging plasma fluid stream tocontainer 21. In that instance, upon the emergence of the buffy coat andthe keying of the BUFFY COAT data entry switch 44, the central controlmeans diverts the emerging buffy coat into container 22. By means ofvalve 16c, again keeping track of its volume.

The collection of the buffy coat will preferably continue in accordancewith both the predetermined buffy coat volume as well as the number ofcycles, another condition predetermined by the physician. If this mostpreferred embodiment is employed, then a representative example might beas follows. Asume, that the predetermined volume and cycle conditionsare set as follows: 350 mls of plasma, 250 mls of buffy coat, and 5cycles. In each cycle, the apparatus will collect 250/5 or 50 mls ofbuffy coat before ending the cycle and thereupon emptying the centrifugebowl and returning all nonleukocyte fluids, predominantly etythrocytesand perhaps excess plasma, to the patient. Prior to the collection ofthe 50 mls, plasma will emerge from the centrifuge and will be collectedin container 22 either until the full 350 mls are collected or, untilthe buffy coat emerges.

During the next cycle, the central control means will direct the furthercollection of plasma, if needed, in order to reach the 350 mlpredetermined volume and then collect an additional 50 mls of buffycoat. The total volume to be contained within container 22, will thenequal 600 mls and would be indicated on display 46 as it is accumulated.

Thus, the instant invention serves to automatically keep track of thevolumes as they are collected thereby facilitating the institution of aconvenient number of cycles whereby the removal of large blood volumesfrom the patient is avoided. Not only is patient safety enhancedthereby, but the automated nature of the procedure further increasessafety since, in accordance with the programmed conditions supplied tothe central control means, the operator need not attempt to keep trackof plasma and leukocyte enriched volumes collected, while still beingassured that the final solution for treatment will contain thepredetermined and desirable leukocyte concentration.

The foregoing described automated methods used in the photopheresisapparatus described with respect to FIG. 1 advantageously employ theinstant invention, in particular a removable and disposable irradiationchamber-pump block for containing the patient fluids/cells andphotoactivatable agent for exposure to photoactivating radiation fromthe light array assembly.

With specific reference to FIGS. 4 and 5, the most preferred arrangementof the irradiation chamber-pump block combination is shown. Irradiationchamber 513 comprises a serpentine pathway 503 for conducting patientfluid from inlet line 501 and presenting the patient fluid in a physicalarrangement having a large surface area to volume ratio. Thus,self-shielding effects of the cells is reduced while the cells arephotoactivated by irradiation impinging upon both sides of serpentineportion 512 by the light array assembly. After photoactivation, thefluid leaves pathway 503, enters outlet tube 511 which is threadedthrough pump block 504 along arcuate pump race portion 508 and outlet502. Arcuate pump race 508 engages a roller pump mechanism (see FIG. 2)for creating peristaltic flow through inlet 501, pathway 503, and outlet502. Shoulder means 509 prevent creep of outlet tubing 502 duringpumping action. Slots 507 are provided for engagement with assistancelevers associated with the patient treatment system. The assistancelevers are activated by the treatment system's central control processorfor urging the irradiation chamber 513, and more particularly, thearcuate pump race 508 of pump block 504 against the compressive forcesexerted by the rollers of pump 203 (see FIG. 2). During such engagement,electrical contact is made between the treatment system and temperatureprobe 213 [more fully described in U.S. Ser. No. 834,294], and fingercontacts 505 electrically connected to electronic memory device 506.

The serpentine pathway portion 512 is preferably formed by bondingtogether in sealing arrangement male and female thin plate sections.Such sections are preferably comprised of a material ideally transparentto the wavelength of photoactivating radiation. In the case ofultraviolet A radiation, polycarbonate has been found most preferredalthough other materials may be employed. Similarly, many known methodsof bonding may be employed and need not be expanded on here. Theirradiation chamber 513 optionally comprises periodic protrusions withinthe track holding outlet tubing 502 for restraining same in securefashion. Pump block 504 may be molded as part of the serpentine pathwaysection 512 or optionally out of separate materials and subsequentlymounted to section 512 as convenient.

In the most preferred embodiment and as additionally described incopending patent application Ser. No. 834,293, fully incorporated hereinby reference, a integrated circuit memory device 506 is installed on acircuit board affixed to chamber 513 for retaining encoded informationspecific for the particular chamber such as type, serial number,certification number, manufacturing site, and, if applicable, priorusage. the memory device is electronically connected to the centralcontrol processor of the patient system by finger contacts 506 whichelectrically engage contact sockets (not shown) described more fully inU.S. Ser. No. 834,259.

As may be apparent, numerous advantages are obtained by the presentinvention. The irradiation chamber-pump block combination comprises arigid and easily handled assembly requiring no additional structuralelements thus providing maximum ease of handling and assembly at minimumcosts. The chamber can be installed in one simple plug-in step therebyfacilitating treatment by less trained personnel particularly sincefluid connections are easily made and procedures for routing tubinglines through peristaltic pumps are obviated. The thickness of theirradiation chamber will ideally be determined in accordance with thestrength of the photoactivating radiation, a predetermined level ofphotoactivating efficiency based on the type and concentration of thedrug, and the patient fluid to be treated. Advantageously, theincorporated memory device provides information for the central controlprocessor of the apparatus to determine authenticity and suitability ofthe chamber for use thereby assuring patient safety. The memory devicecan also identify variations in the type of treatment to be effectedbased on the fluids to be treated.

Upon study of the accompanying figures, and the foregoing description,it will become readily apparent to the skilled artisan that numerousalternatives may be made to the foregoing such as different number orwidth of pathways in the chamber, or utilizing a different mechanicalconfiguration of the pump block, etc. without departing from either thespirit or scope of the instant invention.

What is claimed is:
 1. A flat plate irradiation chamber, for use in apatient treatment system for altering cells, including treating thecells with a photoactivatable agent and passing the cells and the agentthrough a field of photoactivating radiation whereby said agent iscaused to be activated and to affect said cells, said agent and saidcells being contained in the irradiation chamber during irradiation,said flat plate irradiation chamber comprising:a rigid top sheet matablyjoined with a rigid bottom sheet, forming therebetween a rigidserpentine pathway for conducting said cells through said field ofradiation; and pump block means for holding tubing means in fluidcommunication with said serpentine pathway and adapted for engaging aperistaltic pump whereby rotation of the pump causes said cells to flowthrough said serpentine pathway, and wherein said chamber is removablefrom said system and disposable.
 2. The chamber of claim 1 wherein atleast one of said sheets is substantially transparent to saidphotoactivating radiation.
 3. The chamber of claim 2 which furthercomprises means for preventing creeping movement of said tubing meansduring rotation of said peristaltic pump when said pump block means isengaged therewith.
 4. The chamber of claim 2 further comprising memorymeans for providing information characteristic of said chamber to saidpatient treatment system.
 5. The chamber as described in claim 4 furthercomprising sensor probe means in thermal communication with said fluidfor providing an output in response to fluid temperature.
 6. The chamberof claim 4 further comprising means for receiving urging force from saidpatient treatment system for engaging said pump block means with saidperistaltic pump.
 7. The chamber of claim 4 wherein said memory means isselected from the group consisting of integrated circuit having anon-volatile memory, integrated circuit having a power source, andmagnetic memory means.
 8. An irradiation chamber for use in a system fortreating blood, comprising:a serpentine portion comprising two flat,closely spaced apart rigid plates having walls therebetween defining arigid serpentine pathway between the plates, having an inlet and anoutlet, said outlet in flow communication with flexible tubing; and apump block, integral with said serpentine portion for containing saidtubing, comprising a pump track along which is emplaced said tubing forpumping engagement with a pump when said irradiation chamber is insertedinto said system;whereby said irradiation chamber may be inserted intosaid system without the need for a separate step to establish flowcommunication between the inlet of said serpentine chamber and saidflexible tubing and wherein said irradiation chamber may be removed fromthe system together with all blood contacting elements.
 9. The chamberof claim 1, wherein the cells are presented to the irradiation in aserpentine pathway having a large surface area to volume ratio therebyreducing cellular self-shielding effects.
 10. The chamber of claim 1,wherein the top and bottom sheets are male and female thin platesections bonded together in sealing arrangement.
 11. The chamber ofclaim 1, wherein the pump block is molded as part of the serpentinepathway.
 12. The chamber of claim 1, wherein the pump block isseparately mounted to the serpentine pathway.
 13. The chamber of claim1, wherein after mating, the distance between the top and bottom sheetsis about 0.04 inches.
 14. The chamber of claim 1, wherein the rigidplates are polycarbonate.
 15. In combination, a system for treatingblood and an irradiation chamber for use therein, wherein:said systemcomprises a pump, means for treating blood and means for receiving thechamber; and said chamber comprises a rigid top sheet matably joinedwith a rigid bottom sheet, forming therebetween a serpentine pathway forconducting said blood; and pump block means for holding tubing means influid communication with said serpentine pathway and adapted forengaging a peristaltic pump whereby rotation of the pump causes saidblood to flow through said serpentine pathway, and wherein said chamberis removable from said system and disposable.
 16. The combination ofclaim 15, wherein the blood in the serpentine pathway has a largesurface area to volume ratio.
 17. The combination of claim 15, whereinthe top and bottom sheets of the chamber are male and female thin, platesections bonded together in sealing arrangement.
 18. The combination ofclaim 15, wherein the distance between the top and bottom sheets aftermating is about 0.04 inches.
 19. The combination of claim 15, whereinthe rigid sheets are polycarbonate.